In the field of drug research, chemists search for the optimal experiment conditions (e.g., reagents, temperatures) that will lead to the purest material. The route most often chosen involves purification of the drug substance via the generation of a crystalline form of that same drug substance. It is well known that a drug may have the potential to crystallize in a number of different forms. These forms differ in the spatial orientation of the drug molecule in the unit cell of a crystal lattice and possibly the inclusion and location of solvent molecules within the lattice structure. Significant research activity is employed to evaluate the way in which a drug substance crystallizes. Reason being, the crystal form of a drug can significantly influence i) how quickly it can dissolve, ii) how stable it will be, and iii) how easily it can be manufactured into a formulation. If a drug does not dissolve in the appropriate region of the body, then the body cannot properly absorb it and the likelihood of the drug reaching its target is compromised. If a drug is not stable, the shelf-life of the product may be reduced. If the drug cannot be easily manufactured into a formulation, the development costs may increase significantly.
The protocol for screening crystal forms may generally involve: (1) dissolving the drug in a solvent medium, (2) evaporating solvent, cooling the drug/solvent mixture, or adding an antisolvent to increase the degree of supersaturation of the drug in the solvent medium and (3) characterizing the resulting products using techniques such as polarized light microscopy, thermal analysis, Raman spectroscopy, and X-ray powder diffraction. Determining the amount of drug dissolved in the solvent medium provides a means of classifying the solvating power of the solvent. This information is useful in subsequent crystallizations. In order to produce the most suitable crystal form, hundreds or even thousands of individual experiments may have to be conducted. Unfortunately, most of the screening must be performed manually. Thus, the process remains quite time consuming and labor intensive.
Accordingly, those skilled in the art appreciate the need for increased automation of the process of screening for crystal forms in order to reduce the degree of human intervention required by the process and to improve the accuracy, efficiency, reliability and repeatability of the process. Also recognized is the need for a single apparatus that integrates preparation, growth and in situ analysis of crystal forms. The present invention, as described hereinafter in the context of preferred embodiments and processes, is provided to meet these needs.